The Biophysical Therapies Program has the following broad goals: (a) to develop novel cancer treatment strategies based on biophysical principles, especially light and heat, (b) to understand their molecular and cellular mechanisms, (c) to bring them to clinical fruition by facilitating interactions with clinicians and clinician scientists, and (d) to provide a training ground for these novel treatment approaches. Guided by the unifying theme of oxidative and thermal stress, the target mechanisms of the therapies being developed, three inter-related programmatic themes have been developed: 1) Rational Treatment Design and Optimization of novel cancer therapies employing biophysical principles; 2) Immune Modulation based on these therapies; and 3) Molecular Mechanisms of Oxidative and Thermal Stress. The Program is co-led by Barbara Henderson, PhD, a research scientist with long-standing interest in photodynamic therapy and strong familiarity with all research components of the Program and Allan Oseroff, MD, PhD, and Thomas Dougherty, PhD, who respectively lead the clinical translation of dermatologic and non-dermatologic applications of novel therapies. The Program is comprised of 16 members whose peer-reviewed funding is $2.3 M (direct) and total direct funding exceeds $3.8 M. Of its 148 cancer-related publications, 59% are CCSG interactive. The Program has a strong, proven translational research capability as well as an active biotechnology transfer component. Preclinical findings have been translated into 16 ongoing clinical trials. During the past three years, the Program has recruited five new members and ongoing recruitment focuses on strengthening the developing research theme of molecular mechanisms of oxidative and thermal stress.